This study aimed to develop floating tablets of sitagliptin using guar gum to prolong its gastric retention time. Various tablet formulations were prepared using different polymers and evaluated. The optimized formulation F9 containing guar gum, sodium bicarbonate, citric acid, microcrystalline cellulose and magnesium stearate demonstrated the desired pre-compression and post-compression properties including floatation for up to 12 hours. In vitro drug release studies showed this formulation can sustain drug release in the stomach to improve sitagliptin absorption. Overall, the results suggest floating tablets using guar gum are a promising approach for achieving gastric retention.

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Available online at www.icjpir.com ISSN: 2349-5448
Intercontinental journal of pharmaceutical
Investigations and Research
ICJPIR |Volume 3 | Issue 1 | Jan – Mar- 2016 Research Article
Formulation and evaluation of sitagliptan floating tablets
M. Sambasiva rao, A. Sunil kumar reddy, A. Ashok Kumar
Professor & HOD OF Vijaya college of pharmacy, Munaganur (village), Hayathnagar (Mandal),
Ranga redy (District), Pin-501511
Corresponding Author: A. Ashok Kumar
Email: ashok576@gmail.com
ABSTRCT
Gastro retentive dosage form using Guar gum was prepared to develop floating tablets of Sitagliptin that could
retain in the stomach for longer periods of time delivering the drug to the site of action, i.e., stomach. The pre -
compression parameters of all formulations showed good flow properties and these can be used for tablet
manufacture. The post-compression parameters of all formulations were determined and the values were found
to be satisfactory. From the drug content and in-vitro dissolution studies of the formulations, it was concluded
that the formulation F9 i.e. the formulation containing guargum, Sodium bicarbonate, citric acid, micro
crystalline cellulose and Magnesium stearate is the best formulation. As a result of this study it may be
concluded that the floating tablets using a guar gum in optimized concentration can be used to increase the GRT
of the dissolution fluid in the stomach to deliver the drug in a sustained manner. The concept of formulating
floating tablets of Sitagliptin offers a suitable and practical approach in serving desired objectives of gastro
retentive floating tablets.
Keywords: Guar Gum, Sodium Bicarbonate, Citric acid
INTRODUCTION
Gastroretentive drug delivery systems
Gastro retentive drug delivery is an approach to
prolong gastric residence time, thereby targeting
site-specific drug release in the upper
gastrointestinal tract (GIT) for local or systemic
effects. Gastro retentive dosage forms can remain
in the gastric region for long periods and hence
significantly prolong the gastric retention time
(GRT) of drugs.5
Floating systems or hydrodynamically
controlled systems are low-density systems that
have sufficient buoyancy to float over the gastric
contents and remain buoyant in the stomach
without affecting the gastric emptying rate for a
prolonged period of time.6
Comprehensive knowledge about GI dynamics
such as gastric emptying, small intestine transit,
colonic transit, etc. is the key for the designing of
oral controlled release dosage forms. The rate and

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extent of drug absorption from different sites of GI
tract and factors that govern the absorption further
assist the design of dosage form.
Basic Gastrointestinal Tract Physiology
It is well recognized that stomach may be used
as “depot” for sustained-release (SR) dosage forms,
both in human and veterinary applications.7
The
stomach is anatomically divided into three parts:
fundus, body, and antrum (pylorus). The proximal
part made of fundus and body acts as a reservoir for
undigested material, whereas the antrum is the
main site for mixing motions and act as a pump to
accomplish gastric emptying. The process of gastric
emptying occurs during fasting as well as fed
states; however, the pattern of motility differs
markedly in two states. In the fasted states, it is
characterized by inter digestive series of electrical
events, which cycle both through stomach and
intestine every 2 to 3 hrs. This is called the
interdigestive myloelectric cycle or migrating
myloelectric cycle (MMC), which is further divided
into following four phases:
Phase I (basal phase)
Lasts from 40 to 60 min with rare contractions.
It is characterized by lack of any secretary and
electrical activity and contractile motions.
Phase II (preburst phase)
Lasts for 20 to 40 min with intermittent action
potential and contractions. Bile enters the
duodenum during this phase, while the gastric
mucous discharge occurs during the later part of
phase I and throughout the phase III.
Phase III (burst phase)
Lasts for 10 to 20 min. It includes intense and
regular contractions for short period. It is due to
this wave that all the undigested material is swept
out of the stomach down to the small intestine. It is
also known as the “housekeeper wave”.
Phase IV (transition period)
Lasts for 0 to 5 min and occurs between phase
III and phase I.8
AIM AND OBJECTIVE
Aim
The aim of the present study is to formulate and
evaluate Sitagliptin floating tablets.
The objective of the present study is given below:
1. To carry out compatibility studies for the
possible drug/polymer interactions using FTIR
spectral studies.
2. To develop sustained release floating (gastro-
retentive) tablets.
3. To evaluate the formulated dosage forms.
4. Reduction in fluctuation in therapeutic level.
5. To increase in the gastric residence time.
6. To reduce chances of degradation of drug
METHODOLOGY
Preparation of calibration curve for
sitagliptin
Standard curve in 0.1n HCL
Stock Sample Preparation
Accurately weighed 100 mg of drug was first
dissolved in100 mL of 0.1N HCL in 100 mL of
volumetric flask to make a concentration of 1000
μg/mL (primary stock solution). 5 mL of primary
stock solution was pipetted out into 50 mL of
volumetric flask and volume was adjusted with
0.1N HCL to make a concentration of 100μg/mL
(secondary stock solution).
Sample Preparation
From the secondary stock solution pippetout
0.25,0.5,0.75,1,1.25 and 1.5 in to 10ml of
volumetric flask and volume made up to with 0.1N
HCL to give various concentrations such
as5,10,15,20,25,30 μg/mL were prepared for
calibration curve. Standard curve was plotted by
taking absorbance of secondary stock solutions in
UV double beam spectrophotometer at 288 nm.
Formulation of floating tablets of Sitagliptin
by direct compression method
Floating tablets of Sitagliptin were prepared by
direct compression method employing sodium
bicarbonate as gas-generating agent and citric acid
for supporting floating agent. HPMC, xanthum
gum, guar gum were used as rate controlling
polymers. The concentrations of the above

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ingredients were optimized as shown in below table
on the basis of trial preparation of the tablets. All
the ingredients were weighed accurately. The drug
was mixed with the release rate retarding polymers
and other excipients, except magnesium stearate, in
ascending order of their weight. The powder mix
was blended for 20 min to have uniform
distribution of drug in the formulation. Then,
magnesium stearate was added and mixed for not
more than 1 min (to ensure good lubrication.)
About 350 mg of the powder mix was weighed
accurately and fed into the die of single punch
machinery and compressed using 16*8mm punche.
The hardness of the tablets was adjusted at 7-8
kg/cm2
using a Monsanto hardness tester.
RESULTS AND DISCUSSION
Table.1: Formulations of Sitagliptin Floating Tablets (in mg) by Direct compression
Ingredients (mg) F1 F2 F3 F4 F5 F6 F7 F8 F9
SITAGLIPTIN 100 100 100 100 100 100 100 100 100
HPMC 105 122.5 140 -- -- -- -- -- --
XANTHUM GUM -- -- -- 70 87.5 140 -- -- --
GUAR GUM -- -- -- -- -- -- 70 87.5 140
MCC 42 24.5 7 77 59.5 7 77 59.5 7
NaHCo3 35 35 35 35 35 35 35 35 35
Citric acid 12 12 12 12 12 12 12 12 12
Mg. STEARATE 6 6 6 6 6 6 6 6 6
Total Weight 350 350 350 350 350 350 350 350 350
Preparation of standard curve
Table no: 2 Calibration Curve Data of Sitagliptin
CONCENTRATION (µg /ml) ABSORBANCE
0 0
2.5 0.046
5 0.088
7.5 0.124
10 0.161
12.5 0.203
15 0.246

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Fig :1 calibration cuve plot of Sitagliptin
Fourier transformer infrared spectroscopy
By correlating Sitagliptin peaks of pure drug
spectrum with physical- mixtures of the optimized
formulation it was found that the drug is
compatible with the formulation components.
Fig No:2FTIR Spectra of Sitagliptin
y = 0.0161x + 0.0035
R² = 0.9989
0
0.05
0.1
0.15
0.2
0.25
0.3
0 2 4 6 8 10 12 14 16
absorbance
CONC IN µg/ml

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Fig No: 3FTIR Spectra of Sitagliptin optimized
Table no: 3PRE COMPRESSION PARAMETERS:
Formulation
code
Bulk density
(g/cc)
Tapped density
(g/cc)
Carr’s Index Hausner Ratio Angle of repose(θ)
F1 0.45±0.045 0.52 ± 0.09 15.60±0.2 1.15±0.02 28.06 0.31
F2 0.45±0.045 0.50 ± 0.07 12.23±0.6 1.11±0.04 27.58 0.15
F3 0.44±0.044 0.50 ± 0.09 12.58±0.8 1.13±0.08 28.44 0.11
F4 0.45±0.045 0.52 ± 0.04 15.19±0.1 1.15±0.06 28.36 0.13
F5 0.44±0.044 0.52± 0.01 15.48±0.6 1.18±0.08 28.52 0.19
F6 0.45±0.045 0.51 ± 0.04 13.48±0.8 1.13±0.09 29.32 0.19
F7 0.51±0.045 0.59 ± 0.04 14.48±0.8 1.15±0.09 29.69 0.19
F8 0.45±0.045 0.50 ± 0.07 12.23±0.6 1.11±0.04 27.58 0.15
F9 0.45±0.045 0.52 ± 0.04 15.19±0.1 1.15±0.06 28.36 0.13
Sitagliptin floating tablets were prepared by
direct compression method using 16*8mm punch,
adjusting the hardness between 7-8 kg/cm2
. All the
tablets white in color, round with smooth surfaces.
All the formulations were evaluated for bulk
density, tapped density, % compressibility,
hausner’s ratio and angle of repose. The results of
% compressibility, hausner’s ratio and angle of
repose were found to be <16, <1.25 and <30
respectively. These results show that the
formulations have very good flow properties.

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Table.:4 Data for post compression parameters of tablet formulations (F1-F9)
Formulation Code Weight Variation (mg) Thickness (mm) Hardness (kg/cm2
) Friability (%)
F1 344±1.36 3.28±0.20 7.3±0.54 0.72±0.41
F2 348±2.02 3.33±0.22 7.5±0.75 0.37±0.42
F3 350±1.89 3.28±0.17 7.6±0.45 0.40±0.38
F4 347±1.99 3.16±0.05 7.9±0.25 0.46±0.36
F5 348±2.49 3.84±0.17 7.3 ±0.44 0.32±0.25
F6 347±1.99 3.92±0.25 7.6±0.31 0.30±0.17
F7 349±0.89 3.80±0.80 7.6±0.40 0.36±0.20
F8 350±1.88 3.82±0.20 7.5±0.55 0.31±0.25
F9 346±1.15 3.98±0.66 7.7±0.57 0.34±0.36
Table.:5 Data for post compression parameters of tablet formulations (F1-F9)
Formulation Code Drug content (%) Floating
lag time
Swelling index
(%)
Floating duration
(hrs)
F1 98.78±0.24 46sec 32.12 6.3
F2 97.70±0.38 52sec 34.26 8.1
F3 99.51±0.32 59sec 36.01 9.2
F4 99.94±0.21 4min 34.95 8.3
F5 98.42±0.28 6min 37.23 10.1
F6 98.91±0.23 7min 38.18 11.0
F7 98.58±0.24 12sec 36.55 10.3
F8 99.26±0.44 28sec 37.75 11
F9 99.12±0.32 36sec 39.66 12
The tablets were evaluated for weight variation,
thickness, hardness, friability, swelling index,
floating lag time, floating duration, drug content
and in- vitro drug release study. All the
formulations passed the evaluation tests and
showed comparable satisfactory results.
The thickness of all tablets was found to be in
the range of 3.16-3.98 mm and hardness was found
to be in the range of 7-8kg/cm2
in all the
formulations, the MCC and guar gum together
showed good binding properties.
In all the formulations, the %friability was
(0.31-0.72) below 1% as per USP.
The average weight was found to be 344-350
mg which will be within the given limits. Hence all

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the tablets were found to show less weight
variation.
The drug content of all formulations ranged
from 97% to 99%, which is within the specified IP
limits.
Swelling index was found to range from 30% to
40%, which shows that the formulations swell to a
certain degree after coming in contact with the
simulated gastric medium. Also the swelling index
of tablets containing The results of formulations
containing Guargum showed more values of
swelling index than that of the ones containing
xanthum and HPMC respectively because of the
fact that the Guar gum showed good swelling
properties in the later periods of time and that the
CO2 evolved by NaHCO3 was entrapped by the fast
hydrating polymer, thus maintaining the tablet
integrity for longer periods of time, enhancing the
floating duration time to be 12 hrs.
The floating lag time of the dosage forms made
of guar gum and 10% of gas evolving agent were
found to be satisfactory and were <1 min because
guargum is a hydrophilic polymer and that it swells
fast when it comes in contact with 1.2 pH acidic
buffer. But the tablets made of HPMC, xanthum
gum in increasing order of lag time showed lesser
FLTs as its viscosity is less and that the polymer
took even lesser time to form a matrix that could
accommodate the evolved gas and also the
entrapped gas bubbles during compression are more
than that or the gas bubbles in matrices of guargum,
a more viscous polymer. The tablets containing
Guar gum alone showed longer FLT as the tablets
tend to disintegrate due to the fast release of CO2
gas. Guar gum were such that the gas released by
the bicarbonate could facilitate the floating of the
tablets, which was aided by the fast matrix forming
polymer and highly viscous gel forming polymer
(Guar gum) at the later stage of the drug
dissolution, which is evident in the tablets showing
a floating duration up to 12 hrs.
In vitro dissolution profile data of all the
formulations
For gastroretentive formulations generally 0.1N
HCL was used as dissolution medium and for
present formulations 900ml 0.1N HCL as
dissolution medium, USP Type 2 paddle apparatus,
and 5ml samples were withdrawn for every time
point.
Table: 6 Dissolution data of formulation F1-F9
Time (hrs) F1 F2 F3 F4 F5 F6 F7 F8 F9
1 31 28 26 21 18 16 20 16 13
2 40 35 33 35 33 32 35 32 28
3 52 46 45 42 41 38 42 40 36
4 73 65 59 55 52 50 55 52 50
5 85 77 72 69 65 63 67 66 62
6 98 85 83 83 74 76 76 73 68
8 - 95 91 94 83 80 88 82 75
10 - - 94 - 97 90 99 94 89
12 - - - - - 92 95 97

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Fig no:4 Dissoulation graph for F1 – F3
Fig no:5 Dissolution graphs for F4-F6
0
20
40
60
80
100
120
0 1 2 3 4 5 6 8 10 12
%CDR
time in hrs
F1
F2
F3
0
20
40
60
80
100
120
0 1 2 3 4 5 6 8 10 12
%CDR
time in hrs
F4
F5
F6

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Fig no:6Dissolution graphs for F7-F9
The % Cumulative drug release of all the
formulations F1, F2,F3, F5, F6 were not sustained
the drug release for 12 hrs. F4, F7 and F8
formulations showed good integrity for 10 hrs. F9
formulation was optimised based on the floating
behaviour. The optimized formulation F9 showed a
%drug release of 97% for 12 hrs which shows
greater release compare to all other formulation.
Kinetic modelling and mechanism of drug
release
The results of kinetic equations applied to
dissolution profiles of optimized batch F9 were
determined as follows.
TABLE.7: Kinetic values obtained from different plots of F9 formulation
ZERO FIRST HIGUCHI PEPPAS
% CDR Vs T Log % Remain Vs T %CDR Vs √T Log C Vs Log T
Slope 7.971202304 -0.11465774 30.35961017 1.308499573
Intercept 11.14686825 2.115093439 -9.78941327 0.761137851
Correlation 0.972099715 -0.96315767 0.985702545 0.846467921
R 2 0.944977857 0.927672697 0.971609507 0.716507941
CONCLUSION
The post-compression parameters of all
formulations were determined and the values were
found to be satisfactory. From the drug content and
in-vitro dissolution studies of the formulations, it
was concluded that the formulation F9 i.e. the
formulation containing guargum, Sodium
bicarbonate, citric acid, micro crystalline cellulose
and Magnesium stearate is the best formulation. As
a result of this study it may be concluded that the
floating tablets using a guar gum in optimized
concentration can be used to increase the GRT of
the dissolution fluid in the stomach to deliver the
drug in a sustained manner.
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F8
F9

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